Adhesives, their preparation and use

ABSTRACT

Skin friendly pressure sensitive adhesives in the form of inherently tacky polyurethane-containing gells may be prepared by reacting an isocyanate prepolymer, which is itself the reaction product of poly-functional isocyanate and polyoxyalkylene diol monoalkyl ether, with a hydroxyl-containing ester of acrylic or methacrylic acid and optionally other hydroxyl containing compounds and then cross-linking the polymer so formed by means of irradiation. The proportion of acrylate chosen is such that it will react with at least 15 to 25% of the free isocyanate groups in the prepolymer and the remainder react with the other hydroxyl containing compound. The adhesives are capable of absorbing up to 95%, typically from 35 to 95% by weight of water when hydrated. The use of the adhesive in highly moisture vapor permeable dressings is also disclosed.

This is a continuation of Ser. No. 129,526, filed Dec. 7, 1987, nowabandoned.

The present invention relates to an adhesive which is suitable for useon skin and which comprises polyurethane polymer which is capable ofabsorbing water.

Conventionally adhesives employed for skin contact have comprisedsynthetic polymer adhesives such as polyacrylates or polyvinyl alkylethers. Disadvantages associated with the use of this type of adhesiveare known. Polyacrylate adhesives may, for example, occasionally causeskin irritation and maceration a condition which may be worsened if theadhesive is left in contact with the skin for long periods, as forexample, when used on so-called intravenous dressings for coveringcannula sites and the like. A further disadvantage which may arise withthin film dressings is that although the adhesives employed are moisturevapour permeable, the moisture vapour permeability of the adhesive whenpresent as a continuous film is not sufficiently high to permit rapidevaporation of moisture from a dressing which has been applied to anexuding wound, i.e., when the adhesive is in contact with an aqueousfluid. Furthermore, these adhesives are not absorbent to water andindeed may be deleteriously affected by water. The result of using suchan adhesive can be to cause the formation of an unsightly blister whichcan predispose to leakage and so lead to bacterial contamination.

It would be an advantageous therefore if an adhesive could be foundpossessing a high moisture vapour permeability so that it could bepresent as a continuous layer on a dressing for use on an exuding woundand also one which had little propensity to cause irritation even afterprolonged contact with the skin and could also be used, for example, onan intravenous dressing or incise drape.

We have now found an adhesive comprising water absorbentpolyurethane-containing polymer which is suitable for use on the skin.When used in combination with a suitable backing layer for example amoisture vapour permeable, continuous, conformable polymeric film,various types of bacteria-proof adhesive dressing maybe provided whichare conformable to the body surface, absorb exudate when used on exudingwounds while preventing dehydration of the wound, even when exudationhas ceased, so providing a moist environment for improved wound healing,permit inspection of the healing wound, protect the wound frommechanical trauma and can serve as a carrier for topically appliedpharmacologically active agents or medicaments such as antibacterialsand antimicrobials and can remain on intact skin for long periods oftime without deleterious effects. It is particularly surprising that theadhesive properties of the polyurethane are not unduly affected by woundexudate and are satisfactorily maintained when the polyurethane is both`wet` and `dry`. The dressings may remain in place over a wound for aperiod of days yet the dressings maybe removed without causingdiscomfort or compromising the healing wound. It has also been foundthat even on non-exuding wounds, the environment at or near the wound ismaintained in a moist condition which is conducive to wound healing.

United Kingdom Pat. No. 2094809 and U.S. Pat. No. 4505976 describe apressure sensitive adhesive composition which has the capacity to absorbfrom about 15% to 40% its own weight of water. However, the pressuresensitive adhesive per se is not water absorbent. The adhesive containsan additional component which is water absorbent. This is also true ofthe adhesives described in United Kingdom Pat. No. 2008000B.

Accordingly the present invention provides a skin friendly pressuresensitive adhesive which comprises an inherently tacky polyurethane gelwhich adhesive contain both polyurethane and acrylate residues and whichis nots self-adherent.

The polyurethane component of the adhesives of the invention absorbswater e.g., from 5 to 95% of the weight of the adhesive to form a gel,but retains its adhesiveness. While in the form of a gel the adhesiveretains its integrity and does not delaminate from its substrate.

The adhesives of the invention also have the advantage that they arenon-self-adherent so that if for example the adhesive surface becomescreased during the application of a dressing the contacting surfaces ofthe adhesive may be easily peeled apart and the dressing is not wasted.

The gel may be in the form of a layer, film and may contain bubbles andcould even have the appearance of a foam because of such bubbles.However, the gel is most aptly provided in the form of a bubble-freelayer such as a thin film or a thick layer.

The adhesive may be prepared as a wet or dry adhesive. A `wet` adhesivecontains water that is it may be prepared in the presence of an excessof water. A `dry` adhesive is one prepared in the absence of water orwhich may be formed by allowing water to evaporate from a wet adhesive.Such `dry` adhesives may have a water content of less than 5%.

By water absorbent is meant that the polyurethane will absorb water andbecome hydrated and when hydrated may contain up to 95%, typically from35 to 95% by weight of water aptly 50 to 92%, preferably 70 to 90% byweight of water and most preferably 75 to 85% by weight of water.

The water absorption of the adhesive can be obtained by taking a knownweight of the dry adhesive (D) and immersing in water for 24 hours. Thehydrated polymer is removed from the water, surface water is removed bylightly blotting with absorbent paper and then the weight of thehydrated adhesive (W) taken. The water absorption of the adhesive (% byweight) can then be calculated as (W-D) x 100/W.

The polyurethane adhesive may be prepared by reacting isocyanateprepolymer, which itself can be the reaction product of polyfunctionalisocyanate and polyoxyalkylene diol monoalkyl ether, with an acrylatecomprising hydroxyl-containing ester of acrylic or methacrylic acid andoptionally other hydroxyl containing compounds such as water or one ormore polyols whereby the proportion of the acrylate is desirably suchthat it will react with at least from 15 to 25% of the free isocyanategroups in the prepolymer. Any other hydroxyl -containing compoundspresent will react with the remainder of the isocycnate groups. Polymerformed may be cross-linked for example by irradiation.

The other hydroxyl containing compounds may be monools or polyols suchas diols or triols such as primary alcohols but preferably they arepolyoxyalkylene diol monoalkyl ethers as hereinafter defined or othermonools which may confer additional tacky properties to the adhesive.Such monools include hydrogenated mono hydroxylin tackifying resins suchas hydrogenated abietyl alcohol.

Suitable polyoxyalkylene diol mono alkyl ethers for use in forming theprepolymers and polymers employed to prepare the adhesives of thepresent invention include those in which the alkyl group contains from 1to 18 carbon atoms and more suitably 2 to 6 carbon atoms and preferably2 to 12 carbon atoms for example 4 carbon atoms that is the mono alkylether is a monobutyl ether.

Suitably the polyoxyalkylene residue in the mono alkyl ether is ahydrophilic residue that contains polyoxyethylene or polyoxypropyleneresidues or mixtures thereof. Preferred polyoxyalkylene residues arethose which contain a mixture of polyoxyethylene and polyoxypropyleneresidues in a ratio of from 20:80 to 80:20 for example 50:50 and inwhich residues are random randomly arranged with respect to each other.

A preferred polyoxyalkylene diol mono alkyl ether is thereforepolyoxyethylene-polyoxypropylene mono butyl ether in which the ratio ofpolyoxyethylene to polyoxypropylene residues is 50:50 such as Entaroxpolyols available from ICI.

Aptly the molecular weight of the monoalkyl ether is from 3000 to 12000,and more suitably is 4000 to 10000 and preferably is 5000 to 9000. Ithas been found that polyoxyalkylene diol monoalkyl ethers within thismolecular weight range provide polymers which are tacky and suitable foruse on the skin while use of lower molecular weight materials tend toprovide polymers which are not suitable for use as adhesives becausethey are insufficiently tacky.

The polyoxyalkylene diol mono alkyl ethers for use in forming theprepolymer or polymer will normally contain water. It is preferredhowever that the polyoxyalkylene diol monoalkyl ether contains less than1% by weight of water so as to limit the proportion of urea groupsformed in the reaction with the polyisocyanate.

The polyisocyanate used for forming the prepolymer will have afunctionality of greater than 2 and may suitably have a functionality offrom 2.1 to 5 and more suitably from 2.2 to 3.5 and preferably from 2.5to 3.0 for example 2.5, 2.7, 2.85 or 2.9. Suitable polyisocyanatesinclude (cyclo) aliphatic and aromatic polyisocyanates- Preferredpolyisocyanates are aromatic polyisocyanates for example those based ona polymeric methylene di phenyl diisocyanate, for example the Suprasecs(trade mark), which are available from I.C.I. It is preferred that thefunctionality of the isocyanate is not more than 3 as this leads to ahigher cross-link density and is manifest ultimately as a harderadhesive which may not be advantageous for an adhesive which is to beapplied to the skin.

The prepolymers may be simply prepared by heating the two componentstogether in the required proportions at an elevated temperature forsufficient time for the reaction to be completed, for example 90° C. for2 hours, in the presence of a conventional polyurethane polymerisationcatalyst such as 0.2% w/w catalyst of dibutyl tin dilaurate (T12). Themole ratio NCO/OH is suitably from 2.0 to 4.0 in this reaction and theprepolymer so formed contains fom 1.5 to 3.0% by weight offree-isocyanate groups.

The adhesives of the present invention may be prepared by reacting theisocyanate prepolymer described above with hydroxy-containing compoundsa proportion of which also contains an unsaturated functionality whichis reactive when exposed to irradiation for example ultra violet orelectron beam irradiation.

Suitable unsaturated compounds include esters of acrylic or methacrylicacid in which there is at least one hydroxyl functional group which iscapable of reacting with isocyanate present. Preferred esters includehydroxy ethyl methacrylate and methacrylate mono-esters of ofpolyoxylalkylene diols in which the number of repeating ether units isfrom 1 to 25 and preferably 2 to 10, for example 6.

After reaction between the isocyanate prepolymer and thehydroxyl-containing compounds the resulting polymer has thereforependant unsaturated groups which are capable of interacting with eachother to cross-link the polymer under the influence of a polymerisationinitiator and irradiation. One suitable form of radiation is ultravioletirradiation. The polymer may be mixed with a photoinitiator and themixture irradiated by means of ultraviolet radiation. This causes thepolymer to become cross-linked.

The polyurethane polymer so formed is a cross-linked polymer which iscapable of absorbing from 5 to 95% by weight of water depending upon thereactants employed.

Alternatively the adhesive may be formed as a `wet` adhesive bydispersing the uncross-linked polymer and photoinitiator in anappropriate volume of water and then irradiating to form the adhesive.Suitably the wet adhesive may contain from 40 to 65% by weight of water.

In another aspect the present invention also provides a process for thepreparation of skin friendly pressure sensitive adhesive in the form ofan inherently tacky polyurethane-containing gel, typically containingfrom 5 to 95% by weight of water when hydrated which process comprisesreacting an isocyanate prepolymer, which is itself the reaction productof polyfunctional isocyanate and polyoxyalkylene diol monoalkyl ether,with an acrylate comprising a hydroxyl-containing ester of acrylic ormethacrylic acid and polyol in which the proportion of the acrylate issuch that the hydroxyl groups contained therein will react with from 15to 25% of the free isocyanate groups in the prepolymer and cross-linkingthe polymer formed by means of irradiation.

In a further aspect, the present invention provides adhesive productscomprising adhesives in accordance with the invention.

The adhesives of the present invention are suitable for use in a numberof applications. These applications include use as the adhesive whencoated on a substrate for bandages, absorbent dressings, wounddressings, burns dressings, incise drapes, first aid dressings,intravenous catheter dressings, ulcer dressings, ostomy devices, condomattachment in urinary incontinence devices, transdermal drug deliverydevices, electroconductive gels, adhesive tapes (surgical tapes, woundclosure tapes and the like), sanitary protection devices such asnapkins, diapers, incontinence pads and protection pads against physicaltrauma or vibrations. However the main use is envisaged to be indressings and drapes of the types described above when the adhesive isin contact with the skin.

The adhesives of the invention may be employed in the manufacture ofbacteria proof wound dressings such as those which comprise a backinglayer which has upon substantially the whole of one surface thereof alayer of pressure sensitive adhesive in accordance with the invention.Such dressings will typically have a moisture vapour transmission rateof greater than 7000 gm⁻² 24h⁻¹ at 37° C. when the adhesive is incontact with water.

Suitably the adhesive layer may be microscopically continuous over thewhole of the surface of the backing layer.

Many medicinal agents may be incorporated into the adhesives of thepresent invention. By medicinal agents it is meant pharmacologicallyactive agents and agents including topical anaesthetics such asxylocaine, bacteriostatic agents such as silver nitrate; antibacterialagents of which preferred agents are silver sulphadiazine, chlorhexidinesalts, PVP-I, and biguanides antibiotics; topical steroids, enzymes,tissue stimulants, coagulants and anticoagulants and antifungal agents.Other agents such as emollients may be added after the reaction step.

Advantageously water soluble medicaments such as chlorhexidine and itssalts may be dissolved in the water which is used to react with theprepolymer. It is found that chlorhexidine is unaffected during theprocess and the resulting adhesive provides effective release ofchlorhexidine when placed onto the skin.

A suitable method of determining the upright moisture vapourtransmission rate of the dressing of this invention is as follows. Discsof material under test are clamped over Payne Permeability Cups (flangedmetal cups) using sealing rings and screw clamps. The exposed surfacearea of the test sample may be conveniently 10 cm². Each cup containsapproximately 10 ml of distilled water. After weighing the cups areplaced in a fan assisted electric oven maintained at 37±1° C. Therelative humidity within the oven is maintained at 10% by placing 1 Kgof anyhdrous 3-8 mesh calcium chloride on the floor of the oven. Thecups are removed after 24 hours, allowed to cool for 20 minutes andre-weighed. The MVTR of the test material is calculated from the weightloss expressed in units of grams of weight per square meter per 24hours.

A suitable method of determining the inverted moisture vapourtransmission rate of the dressing of this invention is as follows. Themethod described above is employed except that the Payne Cups areinverted in the oven so that the water within the cups is in contactwith the test material and in this case with the adhesive.

EXAMPLE 1

A polyoxyethylene - polyoxypropylene diol monobutyl ether (87.4 g, 0.026moles based on OH value) and a polymeric methylene diphenylenediisocyanate (12.6 g, oaving an isocyanate functionality of 2.5 theNCO/OH=2.5) were mixed together in a 700 cc flange flask fitted with anoverhead stirrer and immersed in a water bath at 90° C. A catalyst ofdibutyl tin dilaurate (0.2% w/w) was added. The mixture was stirred at90° C. for about 2 hours. The isocyanate content of the prepolymer soformed was 1.98%. Sufficient of 2-hydroxyethyl methacrylate to reactwith 20% of the available isocyanate groups was added together with anacrylic polymerisation inhibitor (methoxyethyl hydroquinone) (500 ppm)and then sufficient of the polyoxyethylene -polyoxypropylene diolmonobutyl ether was added to react with the remaining isocyanate groups.The temperature of the mixture was reduced to 60° C. and the mixture wasstirred for about 1 hour. The final product was isolated as a goldenyellow viscous liquid.

A photoinitiator, benzildimethyl ketal (1% w/w) was dispersed in thepolymer and the mixture spread as a layer 2 mm thick between twopolytetrafluoroethylene sheets and irradiated with ultraviolet radiationtypically between 219 and 425 nm. The cross-linked polymer so formed hadadhesive properties and absorbed 82% by weight of water when fullyhydrated.

A thin film of this adhesive as a microscopically continuous layer at aweight per unit area of 70 gm⁻² on a backing layer of a hydrophilicpolyurethane for which polyurethane contains 25% by weight of water whenhydrated, at a weight per unit area of 42 gm⁻² provided an bacteriaproof dressing which has an upright moisture vapour transmission rate of1400 gm⁻² 24h⁻¹ at 37° C. and 100% to 10% relative humidity differenceand an inverted moisture vapour transmission rate of 10500 gm⁻² 24h⁻¹ at37° C.

EXAMPLES 2-4

Adhesives were prepared in a similar manner to Example 1 except that theacrylate used was polypropyleneglycol methacrylate (PPGMM).

    ______________________________________                                               % of NCO   Neutralising                                                       groups     agent for                                                          neutralised                                                                              remainder of  Water absorbency                              Example                                                                              by PPGMM   NCO           (% by weight)                                 ______________________________________                                        2      25         n-butanol     81.6                                          3      20         1-decanol     78.0                                          4      20         polyoxyethylene-                                                              polyoxypropylene                                                              diol mono buthyl                                                              ether         84.0                                          ______________________________________                                    

EXAMPLE 5

An adhesive was prepared in a similar manner to Example 1 except thatthe neutralising agent for the remainder of the isocyanate groups in theprepolymer was hydrogenated abietyl alcohol. The adhesive as formed hasa water absorbency of 85%.

What is claimed:
 1. A skin friendly pressure sensitive adhesive suitablefor use on skin which comprises an inherently tacky polyurethane gelwhich adhesive contains both polyurethane and acrylate residues andwhich is not self-adherent, and which contains up to 95% by weight ofwater when hydrated.
 2. An adhesive according to claim 1 in which theadhesive contains from 35 to 95% by weight of water when hydrated.
 3. Asadhesive according to claim 1 in which the adhesive is a cross-linkedreaction product of an isocyanate prepolymer, which is itself thereaction product of polyfunctional isocyanate and polyoxylalkylene diolmonoalkylether, with an acrylate comprising hydroxyl-containing ester ofacrylic or methacrylic acid and at least one other hydroxyl containingcompound whereby the proportion of the acrylate is such that it reactswith from 15 to 25% of the free isocyanate groups in the prepolymer, theother hydroxyl - containing compound reacting with the remainder.
 4. Anadhesive according to claim 3 in which the acrylate is selected from thegroup consisting of hydroxyethyl methacrylate andmethacrylate-mono-esters of polyoxyalkylene diols in which the number ofrepeating ether units is from 1 to
 25. 5. An adhesive according to claim3 in which in the polyoxyalkylene diol monoalkyl ether the alkyl groupcontains from 2 to 6 carbon atoms and the polyoxyalkylene comprises amixture of polyoxyethylene and polyoxypropylene in a ratio of from 20:80to 80:20.
 6. An adhesive according to claim 2 in which thepolyisocyanate has a functionality of from 2.2 to 3.5.
 7. An adhesiveaccording to claim 3 in which the said other hydroxyl containingcompound is polyoxyalkylene diol monoalkyl ether.
 8. An adhesiveaccording to claim 3 in which the said other hydroxyl containingcompound is a tackifying resin.
 9. An adhesive according to claim 8 inwhich the tackifying resin is hydrogenated abietyl alcohol.
 10. Anadhesive according to claim 1 having an effective amount of a medicinalagent incorporated herein.
 11. A process for the preparation of a skinfriendly pressure sensitive adhesive in the form of an inherently tackypolyurethane gel which process comprises reacting an isocyanateprepolymer, which is itself the reaction product of polyfunctionalisocyanate and polyoxyalkylene diol monoalkyl ether, with acrylatecomprising a hydroxyl -containing ester of acrylic or methacrylic acidin which the proportion of the acrylate is such that the hydroxyl groupscontained therein will react with from 15 to 25% of the free isocyanategroups in the prepolymer and cross-linking the polymer formed by meansof irradiation.
 12. A process according to claim 11 in which at leastone other hydroxyl-containing compound is also present to react with theremaining free isocyanate group.
 13. A process according to claim 12 inwhich the other hydroxyl - containing compound is polyoxyalkylene diolmonoalkyl ether.
 14. A process according to claim 12 in which the otherhydroxyl - containing compound is hydrogenated abietyl alcohol.
 15. Anadhesive product comprising a substrate which contains on one surfacethereof an adhesive according to claim 1.